Sinusitis is one of the most commonly diagnosed diseases in the United States, affecting an estimated 37 million people each year. Studies have demonstrated the major economic impact of this disorder, which can dramatically reduce workplace productivity and quality of life in affected individuals. Patients with chronic sinusitis whose symptoms are most refractory to treatment regimens often develop nasal polyps. Growth of these polyps leads to obstruction of the sinonasal passages, requiring repeated courses of antibiotics to treat underlying infections and steroid therapy to reduce polyp load. In advanced cases, surgery may be necessary to remove the polyps and restore sinus ventilation. Histologically, sinonasal polyps are characterized by proliferation and thickening of mucosal epithelium with focal squamous metaplasia, glandular hyperplasia, subepithelial fibrosis, and stromal edema with numerous blood vessels (Bateman et al. (2003), J. Laryngol. Otol., 117(1):1-9).
Most patients who develop nasal polyps have chronic rhinosinusitis. Nasal airway obstruction and drainage are common presenting symptoms. Anosmia and episodic facial pressure may also be present. A subset of these patients are diagnosed with aspirin-sensitive asthma, also known as Triad asthma and Samter's triad, characterized by the presence of nasal polyps, asthma, and aspirin allergy. When individuals with this disorder take aspirin (or non-steroidal anti-inflammatory drugs in many cases) immediate and severe bronchospasm results, often necessitating treatment in the emergency room. It has been hypothesized that a common stimulus is causing inflammation of both the sinonasal and bronchopulmonary mucosa (Krouse et al. (2007), Otolaryngol. Head Neck Surg., 136(5):699-706).
Currently, treatment of nasal polyps with antibiotics, steroids, allergy shots and even surgery is typically unsatisfactory. Antibiotics require repeated courses and systemic administration, which increases the risk of developing antibiotic resistance and secondary yeast infections. Antibiotics also do not eliminate polyps once they are formed. Steroids reduce but do not eliminate polyps. When given systemically for a long period of time, steroids have many severe side effects including elevation of blood pressure, insomnia, agitation, psychosis, increased susceptibility to infection, easy bruising, weight gain, osteoporosis and joint damage, hyperglycemia and worsening diabetes, cataracts, and muscular weakness. When given intranasally, steroids can cause thinning of the nasal mucosa with subsequent bleeding. In addition, intranasal steroids are not as effective as systemic steroids. Immunotherapy (e.g., allergy shots) is helpful in reducing but not eliminating polyp load in a subset of patients with nasal polyps and evidence of significant allergic triggers. Immunotherapy involves a series of injections (shots) given regularly for several years. Side effects can be severe and include difficulty in breathing, arrhythmia and death. Surgery is used when other medical therapies fail. The risk of surgery includes injury to the eye or brain, spinal fluid leak, loss of sense of smell and nosebleeds in addition to the risks associated with general anesthesia. Furthermore, nasal polyps tend to regrow in at least one-third of patients, often necessitating repeat surgeries.
Thus, sinonasal disease is a problem of major clinical and societal impact for which curative therapeutic modalities are lacking. Microarray technology has revolutionized the field of genetic analysis, making it possible to quantify the simultaneous expression of thousands of genes and is a powerful tool for disease studies. However, prior studies of sinonasal tissue that used this technology focused on subsets of the genome and limited patient populations with upper airway disease (Fritz et al. (2003), J. Allergy Clin. Immunol., 112(6):1057-63; Liu et al. (2004), J. Allergy Clin. Immunol., 114(4):783-90; Benson et al. (2004), J. Allergy Clin. Immunol., 113(6):1137-43; Wang et al. (2006), Ann. Otol. Rhinol. Laryngol., 115(6):450-6; Anand et al. (2006), Am. J. Rhinol., 20(4):471-6; Figueiredo et al. (2007), Am. J. Phinol., 21(2):231-5; Orlandi et al. (2007), Otolaryngol. Head Neck Surg., 136(5):707-13; Bolger et al. (2007), Otolaryngol. Head Neck Surg., 137(1):27-33).